kg] or 2 mg/kg/day [Body weight 40 kg]) as first line treatment of candidaemia and invasive candidiasis in a randomised, double-blind, multinational non-inferiority study in adults and children. AmBisome and Micafungin were administered for a median duration of 15 days. The favourable overall response was 89.5% (170/190) in the AmBisome group and 89.6% (181/202) in the Micafungin group (per protocol analysis set). The paediatric sub-study, which enrolled 98 patients of whom 57 were <2 years old, (including 19 premature infants), showed favourable overall response rates of: 88.1% (37/42) for AmBisome and 85.4% (35/41) for Micafungin (per protocol analysis set).
Invasive zygomycosis: A retrospective analysis covering a 15-year period included 59 patients with haematological malignancies with proven or probable mucormycosis.
Therapy was successful in 16 patients (37%): 9 of 39 patients who received conventional amphotericin B (23%) and 7 of the 12 patients who received AmBisome (58%) responded to therapy.
Go to top of the page5.2 Pharmacokinetic properties
The pharmacokinetic profile of AmBisome, based upon total plasma concentrations of amphotericin B, was determined in cancer patients with febrile neutropenia and bone marrow transplant patients who received 1 hour infusions of 1.0 to 7.5mg/kg/day AmBisome for 3 to 20 days. AmBisome has a significantly different pharmacokinetic profile from that reported in the literature for conventional presentations of amphotericin B, with higher amphotericin B plasma concentrations (Cmax) and increased exposure (AUC0-24) following administration of AmBisome as compared to conventional amphotericin B. After the first dose and last dose, the pharmacokinetic parameters of AmBisome (mean ± standard deviation) ranged from:
C max
7.3 μg/ml (± 3.8) to 83.7 μg/ml (± 43.0)
T 1/2
6.3 hr (± 2.0) to 10.7 hr (± 6.4)
AUC 0-24
27 μg.hr/ml (±14) to 555 μg.hr/ml (± 311)
Clearance (CI)
11 ml/hr/kg (± 6) to 51 ml/hr/kg (± 44)
Volume of distribution (Vss)
0.10 L/kg (± 0.07) to 0.44 L/kg (±0.27)
Minimum and maximum pharmacokinetic values do not necessarily come from the lowest and highest doses, respectively. Following administration of AmBisome steady state was reached quickly (generally within 4 days of dosing). AmBisome pharmacokinetics following the first dose appear non-linear such that serum AmBisome concentrations are greater than proportional with increasing dose. This non-proportional dose response is believed to be due to saturation of reticuloendothelial AmBisome clearance. There was no significant drug accumulation in the plasma following repeated administration of 1 to 7.5mg/kg/day. Volume of distribution on day 1 and at steady state suggests that there is extensive tissue distribution of AmBisome. After repeated administration of AmBisome, the terminal elimination half-life (t½β) for AmBisome was approximately 7 hours. The excretion of AmBisome has not been studied. The metabolic pathways of amphotericin B and AmBisome are not known. Due to the size of the liposomes, there is no glomerular filtration and renal elimination of AmBisome, thus avoiding interaction of amphotericin B with the cells of the distal tubuli and reducing the potential for nephrot
